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Cytokine gene expression of endothelial cells infected with Trypanosoma cruzi
H B Tanowitz1, J P Gumprecht, D Spurr
1Department of Pathology, Albert Einstein College of Medicine, Bronx, NY 10461.
Insights
Trypanosoma cruzi infection significantly increases interleukin (IL)-1 beta, IL-6, and colony-stimulating factor 1 (CSF-1) gene expression in endothelial cells. These findings highlight the role of vascular endothelium-derived cytokines in Chagas
Area of Science:
- Cardiovascular Biology
- Immunology
- Parasitology
Background:
- Coronary microvascular dysfunction and platelet activation are key factors in Chagas' cardiomyopathy.
- The role of the vascular endothelium in Chagas' disease pathogenesis requires further investigation.
Purpose of the Study:
- To investigate alterations in cytokine gene expression in human umbilical vein endothelial cells (HUVECs) infected with Trypanosoma cruzi.
- To determine the contribution of endothelial cell-derived cytokines to Chagas' cardiomyopathy.
Main Methods:
- Northern blot analysis to assess mRNA levels of various cytokines (IL-1 beta, IL-6, CSF-1, c-sis) in infected and uninfected HUVECs.
- In situ hybridization to localize IL-6 mRNA expression within individual infected cells.
- ELISA to quantify IL-6 and IL-1 beta protein levels in cell supernatants and patient serum.
Main Results:
- Interleukin (IL)-1 beta, IL-6, and colony-stimulating factor 1 (CSF-1) mRNA expression significantly increased in T. cruzi-infected HUVECs compared to uninfected cells.
- c-sis mRNA levels decreased with prolonged infection.
- Elevated levels of IL-6 and IL-1 beta proteins were detected in the supernatants of infected HUVECs and in the serum of an acutely infected individual.
Conclusions:
- Trypanosoma cruzi infection induces significant changes in cytokine gene expression in vascular endothelial cells.
- Endothelial cell-derived cytokines, particularly IL-6, may play a crucial role in the pathogenesis of Chagas' cardiomyopathy.
- These findings suggest that targeting endothelial cell-derived cytokines could be a potential therapeutic strategy for Chagas' disease.
Abstract:
Coronary microvascular spasm and platelet hyperreactivity have been implicated in the pathogenesis of Chagas' cardiomyopathy. To clarify further the role of the microvasculature in this disease, alterations in cytokine gene expression due to Trypanosoma cruzi infection of human umbilical vein endothelial cells were examined. Northern blot analysis of total RNA from endothelial cells demonstrated that interleukin (IL)-1 beta, IL-6, and colony-stimulating factor 1 (CSF-1) mRNA expression was absent or minimal in uninfected cells but significantly increased in infected cells. c-sis mRNA levels diminished with increased time of infection. In situ hybridization studies also demonstrated high levels of IL-6 mRNA in individual infected cells. Significant levels of IL-6 and IL-1 beta protein were detected in the supernatants of infected endothelial cells. The serum of an acutely infected individual contained high levels of IL-6 protein, suggesting the potential importance of cytokines secreted by the vascular endothelium in the pathogenesis of Chagas' cardiomyopathy.